ATM mutations in cancer families

Cancer Res. 1996 Sep 15;56(18):4130-3.


Ataxia-telangiectasia (A-T) is a multisystem recessive disease characterized clinically by cerebellar ataxia, oculocutaneous telangiectasias, immunodeficiency, sensitivity to radiomimetic agents, and cancer predisposition. This pleiotropic disorder is caused by mutations in the ATM (mutated in A-T) gene, which is located in the human chromosomal region 11q22-q23. The ATM gene product is a member of a novel family of large proteins implicated in the regulation of the cell cycle and response to DNA damage. Heterozygosity for A-T was previously suggested to be associated with an increased risk of tumors, particularly female breast cancer. Because of loss of constitutional heterozygosity at 11q22-q23 is a frequent event in breast and other tumors, suggesting the presence of a tumor suppressor gene(s) in this region, we screened blood DNA samples from 88 unrelated breast cancer patients of Swedish cancer families for ATM mutations using single-strand conformation polymorphism analysis. All patients had a family history of tumors previously associated with A-T heterozygosity or homozygosity. We demonstrate the first three germ-line mutations in ATM identified by screening of breast cancer patients. Two mutations were previously found in A-T homozygotes and one mutation was a 1-bp insertion. All mutations were found in families with a large number of tumors, however, they did not cosegregate with malignancies. Although the proportion of A-T carriers in this sample seems to be higher than expected by chance, larger studies and pooled data sets will be required to establish that an A-T allele confers cancer susceptibility in heterozygotes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenine
  • Alleles
  • Ataxia Telangiectasia / genetics*
  • Ataxia Telangiectasia Mutated Proteins
  • Breast Neoplasms / genetics
  • Cell Cycle Proteins
  • Chromosome Deletion*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 11*
  • DNA-Binding Proteins
  • Female
  • Genetic Carrier Screening
  • Humans
  • Male
  • Neoplasms / genetics*
  • Pedigree
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Point Mutation*
  • Polymorphism, Genetic*
  • Polymorphism, Single-Stranded Conformational
  • Protein Biosynthesis
  • Protein Serine-Threonine Kinases*
  • Proteins / genetics*
  • Sequence Deletion*
  • Thymine
  • Tumor Suppressor Proteins


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Proteins
  • Tumor Suppressor Proteins
  • Phosphotransferases (Alcohol Group Acceptor)
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases
  • Adenine
  • Thymine